Showing papers in "Epilepsia in 1996"

The clinical course of epilepsy and its psychosocial correlates: findings from a U.K. Community study.

Abstract: Summary: As part of a large community-based study, we retrospectively examined the clinical course of epilepsy in an unselected population of people who had a recent history of seizures or were receiving antiepileptic drugs (AEDs). Clinical information was collected from medical records, and information about psychosocial functioning was obtained by means of postal questionnaires sent to identified subjects. The response rate to the postal questionnaire was 71%. There were some deficiencies in the recording of clinical data, which is not unusual since data were taken from records held by primary physicians rather than from hospital clinics. Nevertheless, findings regarding the clinical course of epilepsy corresponded to those of earlier studies. Fifty-seven percent of the sample had had at least a 2-year seizure-free period and 46% of subjects were currently in a remission of at least 2-year duration. There was a clear relationship between current seizure frequency and levels of anxiety and depression, perceived impact of epilepsy, perceived stigma, and marital and employment status. The relationship of seizure frequency and other clinical variables to psychosocial function was explored by multivariate analysis techniques. The amount of variation in scores on the various measures of function accounted for by the clinical variables was small. The most important predictor was current seizure activity, which was the first variable to enter the regression analyses for six of the eight measures of psychosocial function considered. Age at epilepsy onset also emerged as a significant predictor for depression, stigma, and marital status. In individuals with epilepsy in remission, there was little evidence that psychosocial functioning was associated with length of remission, a finding which may in part reflect the nature of this study population. The results indicate that there are several more important predictors of psychopathology and social dysfunction in epilepsy and suggest several implications for treatment interventions.

Incidence and clinical characterization of unprovoked seizures in adults: a prospective population-based study.

Abstract: In a population-based prospective study of epileptic seizures in adult s aged > 17 years, we identified 563 patients with possible seizures in a period of 34 months. Seizures were unprovoked in 160 patients, an incidence of 56 in 100,000 person-years. There was no difference in incidence between sexes. Age-specific incidences of unprovoked seizures increased sharply in men from age 60 years and in women from age 70 years. The incidence of unprovoked seizures in those aged > 65 years was 139 (men 166, women 116). The cumulative incidence of unprovoked seizures between the ages of 17 and 84 years was 4.6%. The proportion with an identified presumptive cause for unprovoked seizures increased with advancing age. A presumed etiology was identified in 77% of persons aged > 60 years. Stroke was the most common etiology, detected in 30% (incidence 16) and in 45% at ages > 60 years. Tumors were detected in 11% (incidence 6) and Alzheimer's disease was detected in 7% (incidence 4). Eighteen percent of patients were demented. Unprovoked seizures were partial in 68% of cases (incidence 38), and generalized in 16% (incidence 9). Another 13% of patients had generalized seizures, but seizure onset was not witnessed (incidence 7). In 16%, there was a delay of > 1 year from the first unprovoked seizure to initial diagnosis.

A brief questionnaire to screen for quality of life in epilepsy: the QOLIE-10.

Abstract: Summary: Purpose: To evaluate a brief questionnaire to screen aspects of health-related quality of life for persons with epilepsy. Methods: A study of 304 adults with epilepsy was undertaken at 25 seizure clinics in the United States. It was used for derivation of a brief screening tool from a longer instrument (QOLIE-89). Results: The 10–item questionnaire (QOLIE-10) covers general and epilepsy-specific domains, grouped into three factors: Epilepsy Effects (memory, physical effects, and mental effects of medication), Mental Health (energy, depression, overall quality of life), and Role Functioning (seizure worry, work, driving, social limits). Scale scores were significantly different among seizure groups (p = 0.003). Conclusions: The QOLIE-10 can be completed by a patient in several minutes and reviewed rapidly by the physician. This screening tool could provide potentially useful information for initial assessment or follow-up of problem areas that are not commonly evaluated during routine clinical visits with patients with epilepsy.

Incidence of Epilepsy in Childhood and Adolescence: A Population‐Based Study in Nova Scotia from 1977 to 1985

Abstract: Data from a regional EEG laboratory allowed us to identify almost all children in Nova Scotia (population 85,000) with one or more unprovoked, afebrile seizures from 1977 through 1985. We then reviewed hospital and pediatric neurology physician charts to limit cases to those with two or more definite afebrile seizures between the ages of 1 month and 16 years. In all, 693 children developed epilepsy: typical childhood absence seizures (AS) (97), either generalized tonic-clonic (GTCs) or partial seizures either secondarily generalized or not (511), and other generalized seizure types, including infantile spasms (IS) as well as myoclonic, akinetic, tonic, and atypical AS (85). The incidence of epilepsy was 118 in 100,000 for children aged less than 1 year, 48 in 100,000 for those aged 1-5 years, 43 in 100,000 for those aged 6-10 years, and 21 in 100,000 for those aged 11-15 years. The incidence for each year of age between 1 and 10 years was remarkably constant (mean 46 in 100,000 +/- 7 SD). Comparison of the incidence rates showed significant differences for those aged less than one year as compared with all others, and for those aged greater than 10 years as compared with those aged 1-10 years. We conclude that the incidence of epilepsy is highest in the first year of life, plateaus in early childhood, and decreases markedly after age 10 years. The overall incidence of epilepsy in childhood is lower than that reported in previous studies.

Complex Febrile Seizures

Abstract: In the context of a prospective cohort study, we examined the associations between individual complex features of both first (n = 428) and recurrent (n = 240) febrile seizures and factors shown to predict outcome in children with febrile seizures. Thirty-five percent of first and 33% of recurrent febrile seizures had one or more complex features (focal onset, duration > or = 10 min, or multiple seizures during the illness episode). There were strong correlations between focality and prolonged duration for both first and recurrent febrile seizures. A low fever at the time of the seizure was marginally associated with prolonged duration. Most factors associated with either recurrent febrile seizures or subsequent unprovoked seizures were not associated with either the initial seizure being complex or the likelihood that a recurrence would be complex. However, the children with recurrent febrile seizures, complex features tended to repeat. This factor was statistically significant and particularly striking for prolonged duration. Genetic or other constitutional factors may explain why the prolonged feature recurs. Eleven (2.5%) children had three or four risk factors for recurrent febrile seizure that was prolonged. This very small group of children may be candidates for abortive therapy to be administered at the onset of a recurrent seizure.

Localization of Temporal Lobe Foci by Ictal EEG Patterns

Abstract: Summary: Identifying patients whose complex partial seizures originate in temporal neocortex rather than in hippocampus is important because such patients have less favorable outcomes with standard anteromesial temporal resections. We reviewed scalp-recorded ictal EEGs of 93 epilepsy surgery candidates who either underwent intracranial EEG monitoring (n= 58) or who were referred directly for temporal lobectomy (n= 35). We defined seven patterns of early seizure discharges, grouped patients according to their seizure pattern, and correlated these with the site of seizure onset determined by intracranial EEG. Categorization by seizure pattern was also compared with brain magnetic resonance imaging (MRI) findings and intracarotid amobarbital (Wada) testing. An initial, regular 5- to 9-Hz inferotemporal rhythm (type 1A) was most specific for hippocampal-onset seizures. Less commonly, a similar vertex/parasagittal positive rhythm (type 1B) or a combination of types 1B and 1A rhythms (type 1C) was recorded. Seizures originating in temporal neocortex were most often associated with irregular, polymorphic, 2- to 5-Hz lateralized activity (type 2A). This pattern was commonly followed by a type 1A theta rhythm (type 2B) or was preceded by repetitive, sometimes periodic, sharp waves (type 2C). Seizures without a clear lateralized EEG discharge (type 3) were most commonly of temporal neocortical origin. These associations between type of seizure pattern and probable site of cerebral origin were statistically significant. MRI and Wada testing did not have as much specificity as ictal patterns in differentiating among seizure origins. We conclude that the initial pattern of ictal discharge on scalp EEG can assist in distinguishing seizures of temporal neocortical onset from those of hippocampal onset. This information can be used to identify patients for invasive monitoring.

Update on the Mechanism of Action of Antiepileptic Drugs

Abstract: Novel antiepileptic drugs (AEDs) are thought to act on voltage-sensitive ion channels, on inhibitory neurotransmission or on excitatory neurotransmission. Two successful examples of rational AED design that potentiate GABA-mediated inhibition are vigabatrin (VGB) by irreversible inhibition of GABA-transaminase, and tiagabine (TGB) by blocking GABA uptake. Lamotrigine (LTG) prolongs inactivation of voltage-dependent sodium channels. The anticonvulsant action of remacemide (RCM) is probably largely due to blockade of NMDA receptors and prolonged inactivation of sodium channels induced by its desglycinated metabolite. Felbamate (FBM) apparently blocks NMDA receptors, potentiates GABA-mediated responses, blocks L-type calcium channels, and possibly also prolongs sodium channel inactivation. Similarly, topiramate (TPM) has multiple probable sites of action, including sodium channels, GABA receptors, and glutamate (AMPA) receptors. Gabapentin (GBP) apparently has a completely novel type of action, probably involving potentiation of GABA-mediated inhibition and possibly also inactivation of sodium channels. The therapeutic advantages of the novel AEDs are as yet only partially explained by our present understanding of their mechanisms of action.

Double-Blind, Placebo-Controlled Trial of Topiramate as Add-on Therapy in Patients with Refractory Partial Seizures

Abstract: Summary: In a double-blind, randomized, parallel-group trial, we compared topiramate (TPM) with placebo as addon therapy in patients with refractory partial epilepsy. TPM was titrated either to the target dosage of 800 mg/ day [400 mg twice daily (b. i. d.)] or to the maximal tolerated dose if lower. Twenty-eight (28) patients were randomized to each treatment group. In the intent-to-treat analysis, the net median percent reduction relative to placebo in average monthly seizure rate was 54% for patients in the TPM group (p < 0.001). None of the placebo-treated patients and 43% of the patients treated with TPM experienced 250% reduction in seizures (p = 0.001), and 36% of patients assigned to TPM had a 75–100% reduction in seizures (p < 0.01). Secondarily generalized seizures were also significantly reduced in the TPM group (p = 0.044). The most common adverse events (AE) reported in the TPM group were fatigue, impaired concentation, weight loss, dizziness, and paresthesias. AE occurring either during the rapid titration of TPM or at high dosages led 21% of TPM-treated patients to withdraw from the study. Half of these occurred during the titration study period. No serious AE or clinically important changes in clinical laboratory measures were observed. The present study further establishes the favorable profile and good benefithisk ratio of TPM in resistant partial epilepsy.

Cognitive Consequences of Two-Thirds Anterior Temporal Lobectomy on Verbal Memory in 144 Patients: A Three-Month Follow-Up Study

Abstract: Previous studies have shown that left temporal lobectomy for intractable epilepsy can lead to verbal memory deficits. However, patients with left temporal lobe epilepsy (LTLE) frequently have impaired verbal memory preoperatively. The present analysis of 144 patients who underwent temporal lobe resections for either left (n = 68) or right (n = 76) temporal lobe epilepsy (LTLE, RTLE) addressed the questions of (a) whether a left two-thirds anterior temporal lobectomy (ATL) increases deficits in these qualitative aspects of verbal memory already impaired preoperatively, and (b) whether other aspects of verbal memory are additionally affected. We also evaluated possible determinants of preoperative abilities and postoperative changes, using multiple regression analysis. Preoperatively, patients with LTLE differed from patients with RTLE only in poorer performance on measures of long-term consolidation/retrieval (delayed recall). This is related to hippocampal pathology and seizure severity. Only left temporal lobe resections resulted in significant deterioration in verbal learning and memory. Acquisition over learning trials and recognition deteriorated most markedly, whereas performance in long-term consolidation/retrieval showed only minor changes. Preoperative performance levels, chronological age, the extent of the en bloc resection, preoperative performance on figural memory, and preoperative seizure severity were valuable determinants of postoperative changes in acquisition and recognition. In contrast, changes in consolidation/retrieval related only to preoperative ability. Left two-thirds ATL leads to new impairment in addition to preexisting memory deficits. The finding that left temporal lobectomy affects verbal acquisition and recognition more than long-term consolidation/retrieval, including the different determinants of these changes, most likely reflects the differential effects of surgery on mesial temporal and neocortical temporal functions.

Predictors of Intractable Epilepsy in Childhood: A Case‐Control Study

Abstract: Little is known about what factors predict intractable epilepsy at the time of initial diagnosis We performed a case-control study to identify early predictors of medically intractable epilepsy in children Cases were children who had an average of one seizure or more a month over a 2-year period and who, during that time, had failed trials of at least three different antiepileptic drugs (AEDs) Controls were children who had epilepsy, who had been seizure-free for > or = 2 years, and who had never, before becoming seizure-free, met the definition for intractable epilepsy Strong univariate associations were noted between intractability and several factors: infantile spasms (IS) remote symptomatic epilepsy, a history of status epilepticus (SE) before the diagnosis of epilepsy, neonatal seizures, and microcephaly Cases were significantly younger than controls at onset (18 vs 58 years); this was not due solely to cases with onset during the first year of life but was an association apparent throughout the age range studied With multiple logistic regression, independent predictors of intractability were IS, odds ratio (OR) = 1042, p = 003; age at onset with a decreasing risk with increasing age, OR = 077 per year, p less than 00001; remote symptomatic epilepsy, OR = 224, p = 004; and SE, OR = 330, p = 004 These findings complement those of recent cohort studies of remission of epilepsy and provide useful leads for future prospective studies of intractable epilepsy

Postictal Psychosis: A Comparison with Acute Interictal and Chronic Psychoses

Abstract: Summary: We studied 30 patients with postictal psychosis and compared them with 33 patients with acute interictal psychosis and 25 patients with chronic psychosis. All patients had either complex partial seizures (CPS) or EEG temporal epileptogenic foci. Patients with postictal psychosis had a high incidence of psychic auras and nocturnal secondarily generalized seizures. The most striking feature that distinguished postictal psychosis from both acute interictal and chronic psychoses was phenomenological: the relatively frequent occurrence of grandiose delusions as well as religious delusions in the setting of markedly elevated moods and feeling of mystic fusion of the body with the universe. In addition, postictal psychosis exhibited few schizophreniform psychotic traits such as perceptual delusions or voices commenting. Reminiscence, mental diplopia, and a feeling of impending death were also fairly frequent complaints of patients with postictal psychosis. Interictal acute psychosis and chronic epileptic psychosis were psychopathologically similar. Although acute interictal and chronic epileptic psychoses could simulate schizophrenia, postictal psychosis results in a mental state quite different from that of schizophrenic psychosis.

Epilepsy surgery in infants.

Abstract: Summary: Purpose: We report 12 infants who had frontal (n = 3), temporal (n = 2), or temporoparieto-occipital (n = 2) resection or functional hemispherectomies (n = 5) at age 2.5–29 (mean 15.3) months for catastrophic epilepsy due to focal cortical dysplasia (n = 5), Sturge-Weber syndrome (n = 3), ganglioglioma (n = 3), or hemimegalencephaly (n = 1). Seizures began at 1 day to 14 months (mean, 4.0 months) after birth, occurred frequently (often many times per day, and were refractory to antiepileptic drugs. Patients were evaluated for surgery at 2.5–24 (mean 12.4) months of age. Seven patients had hemiparesis and eight had slowed cognitive development. Seizures were characterized by arrest or marked reduction of behavioral motor activity with unclear level of consciousness (n = 4, with temporal or temporoparietal EEG seizures), focal clonic activity (n = 3, with perirolandic EEG seizures), generalized tonic stiffening (n = 3, with temporoparieto-occipital, parietal, or frontal EEG seizures), or infantile spasms and hypsarrhythmia (n = 2, with a frontal tumor or temporoparieto-occipital cortical dysplasia). Methods: Magnetic resonance imaging (MRI) revealed the epileptogenic lesion in all but two patients, both with cortical dysplasia localized by interictal positron-emission tomography (PET) and other clinical or EEG features and confirmed on histopathologic examination of resected tissue. Results: At follow-up 4-86 (mean 32) months after surgery, six patients were seizure free (Engel outcome class I), three had rare seizures with none in at least the previous 6 months (Engel class II), and two had worthwhile improvement (Engel class III). Except for the severely developmentally delayed infant with hemimegalencephaly, several patients had marked “catch-up” developmental progress after class I, 11, or III outcome. Postoperative complications included subdural hematoma over the contralateral hemisphere (one patient) and entrapment and enlargement of the ipsilateral temporal horn (one patient) after hemispherectomy, both corrected uneventfully with a second surgical procedure. One patient died of unexplained causes several hours after frontal lobectomy. No patients had new neurologic deficits after surgery, and one patient had resolution of progressive fluctuating hemiparesis after resection of temporoparieto-occipital cortical dysplasia. Conclusions: Our results agree with previous reports that epilepsy surgery can provide relief from catastrophic epilepsy in carefully selected infants.

Nonconvulsive Status Epilepticus in the Emergency Room

Abstract: Summary: Purpose: The study reviewed emergent cases of nonconvulsive status epilepticus (NCSE) to evaluate causes of diagnostic and management delay and examined frequent diagnostic features suggestive of NCSE. Methods: In a retrospective study, we assessed the clinical presentation of 23 patients with one or more NCSE episodes, their medical history, EEG, and antiepileptic drug (AED) treatment. We also evaluated causes of diagnostic delay in patients referred to the emergency room (ER) in confusional states. Results: There was considerable overlap in clinical features of patients with complex partial SE (CPSE) and generalized nonconvulsive SE (GNSE). Delays in seeking medical attention were common. Diagnosis was significantly delayed in 10 patients. Three cases illustrate the possible markedly different presentations of NCSE. Conclusions: NCSE often goes unrecognized or is mistaken for behavioral or psychiatric disturbance. The pleo-morphic clinical presentation of NCSE indicates that EEG and a therapeutic trial of AEDs afford the best diagnostic measures in acute waxing and waning confusional states associated with agitation, bizarre behavior, staring, increased tone, mutism, or subtle myoclonus.

Empirical techniques for determining the reliability, magnitude, and pattern of neuropsychological change after epilepsy surgery.

Abstract: Summary: Purpose: We assessed test-retest neuropsychological performance in patients with complex partial seizures to derive reliable change indices (RCIs) and regression-based norms for change, indices that may be helpful in assessing cognitive outcome after anterior temporal lobectomy. Methods: Forty patients with complex partial seizures (CPS) who did not undergo epilepsy surgery were administered a comprehensive neuropsychological battery on two. occasions. Their test-retest data were used to compute both RCIs and regression-based norms for change for each neuropsychological index. RCIs corrected for practice effects provide a confidence interval (CI) indicating the degree of performance change required to exceed the variability attributable to sources of error (e.g., practice, test-retest reliability). Regression-based norms for change also correct for several sources of measurement measurement error and examine observed versus expected test-retest changes on a common metric, thereby facilitating determination of the degree and relative magnitude of change across cognitive domains. Results: Mean changes in test-retest performance were generally modest, but were evident across several test measures. Our data indicate a considerable degree of individual variability in test-retest Performance. Conclusions: RCIs and regression-based norms are complementary indexes and can be particularly useful in examining the test-retest performance of individual patients who undergo epilepsy surgery as well as in the more general investigation of cognitive outcome after epilepsy surgery.

Vigabatrin as Initial Therapy for Infantile Spasms: A European Retrospective Survey

Abstract: Summary: Purpose: The efficacy and tolerability of vigabatrin (VGB) as an add-on therapy in the treatment of infantile spasm (IS) prompted physicians to explore its use as the first drug in this seizure type. Methods: Our retrospective study included 250 infants diagnosed with IS; the data obtained were subjected to peer-group review. Of this infant population, 192 infants were considered to have classic IS and had received VGB as their first treatment for the spasms. There was a slight preponderance of boys (57%) in this population. Mean age of IS onset was 5.8 months; 60% had typical hypsarrhythmia. Results: Initial suppression of spasms was obtained in 68% of infants with a median time to response of 4 days at an average VGB dose of 99 mg/kg/day. The best response was seen in those infants with tuberous sclerosis (96% response) and in those younger than 3 months at onset of spasms (90% response). Of these infants, 43 (22%) of 192 subsequently had other types of seizures, and a recurrence of infantile spasms occurred in 28 (21%) of 131 responders. At the end of this study, 96 of 192 infants who could be evaluated were seizure free with VGB monotherapy. Treatment appeared to be well tolerated, with only 33 (13%) infants with adverse events, of which the most common were somnolence (15 patients) and hyper-kinesia (eight patients). In only two cases did adverse events require VGB withdrawal. Conclusion: This study supports the opinion that VGB may be considered an initial treatment for IS regardless of cause.

Adolescents with Active or Inactive Epilepsy or Asthma: A Comparison of Quality of Life

Abstract: Summary: Purpose: We compared quality of life (QOL) in youth with inactive or active epilepsy with that of a similar sample of youth with asthma. We explored 19 different dimensions in three domains (psychological, social, and school) and also determined differences related to illness severity and gender. Methods: Subjects were 228 adolescents (117 with epilepsy and 111 with asthma). Data were collected from clinic records and from the adolescents, their mothers, and their teachers through questionnaires and structured interviews. Data were analyzed by analysis of covariance. Results: The analysis with all 19 QOL variables indicated a significant difference between the total asthma and the total epilepsy samples (multivariate F = 3.36, p = 0.0001). Further evaluation reflected differences between the epilepsy group and the asthma group on 13 of the 19 QOL variables. When active and inactive epilepsy and asthma groups were compared, youth with active epilepsy were faring worse than all other groups in 10 areas. Moreover, youth with inactive epilepsy were faring worse than those with inactive asthma in four areas. Illness severity and sex differences were more strongly related to QOL in the epilepsy sample than in the asthma sample. Sex-severity interactions suggested that girls with high seizure severity were most at risk for QOL problems. Conclusions: Youth with active epilepsy generally had the poorest QOL. Severe seizures and female sex were associated with more problems. Sex-severity interactions should be explored in future research.

The pilocarpine model of epilepsy in mice.

Abstract: Summary: Purpose: To characterize the acute and chronic behavioral, electrographic and histologic effects of sustained seizures induced by pilocarpine in mice. Methods: After status epilepticus, the surviving animals were continuously monitored for 24 h/day for 120 days. The brains were processed by using neo-Timm and Nissl stains. Results: The first spontaneous seizures occurred between 4 and 42 days after status epilepticus. The mean “seizure-silent period” lasted for 14.4 ± 11.9 days. During the chronic phase, recurrent spontaneous seizures were observed 1–5 times per animal per week and were associated with sprouting in the supragranular layer of the dentate gyrus. Conclusions: Structural brain damage promoted by pilocar-pine-induced status epilepticus may underlie or be associated with recurrent spontaneous seizures in mice.

Surgical treatment of extratemporal epilepsy: clinical, radiologic, and histopathologic findings in 60 patients.

Abstract: Summary: Purpose and Methods: The aim of this study was to analyze clinical, radiologic, and histopathologic findings in 60 consecutive patients with medically intractable extratemporal epilepsy who were operated on between November 1987 and May 1993. Results: Histologically, there were distinct structural abnormalities in 50 (83%) of the surgical specimens. Signal abnormalities on magnetic resonance imaging (MRI) were present in all patients with neoplastic lesions (n = 17) and in 94% of patients with nonneoplastic focal lesions (n = 32). Overall, structural abnormalities were detected by MRI in 47 (96%) of 49 patients with focal lesions. During a mean follow-up of 4 years, 30 (54%) patients remained completely seizure free, 11 (20%) had ≤2 seizures per year, seven (12%) showed a seizure reduction of ≥75%, and eight (14%) had <75% reduction in seizure frequency. The fraction of seizure-free patients was 12 (80%) of 15 in patients with neoplastic lesions, 16 (52%) of 31 in patients with nonneoplastic focal lesions, and two (20%) of 10 for those without histopathologic abnormalities. The differences in seizure outcome between patients with and without focal lesions were statistically significant (p < 0.05), if seizure-free outcome was compared with persistent seizures. Conclusions: Focal lesions and particularly neoplasms are associated with improved postoperative seizure control compared with patients without histopathologic abnormalities. We advise caution in considering surgery to treat extratemporal epilepsy in patients who have normal MRI scans, because the outcome with the approach described in this study is poor in such cases.

The National Hospital Seizure Severity Scale: A Further Development of the Chalfont Seizure Severity Scale

Abstract: Seizure severity scales have recently been identified as an important additional outcome measure in trials of new antiepileptic drugs (AEDs). The National Hospital Seizure Severity Scale (NHS3) is presented as a refined version of the Chalfont Seizure Severity Scale. The principal advantages of the new version are that it is quicker and simpler to apply, the limits of reliability are now clearly defined, and construct validity for the scale is available. The scale is administered by a health professional during an interview with a patient and a witness to the seizures. It contains seven seizure-related factors and generates a score from 1 to 27. An intraclass correlation coefficient of 0.90 was obtained during interobserver and test-retest reliability assessment, suggesting that the scale is sufficiently reliable for group studies. Scores for an individual patient should be interpreted with caution in light of the limits of agreement obtained. Validation experiments indicate that NHS3 measures seizure severity in a manner compatible with the subjective impression of people with epilepsy. We suggest that the NHS3 is a valid, easily applicable measure of seizure severity that is acceptably reliable for use in trials of novel AEDs.

Long-term outcome of West syndrome : a study of adults with a history of infantile spasms

Abstract: To our knowledge, ours is the first study to evaluate the outcome of infantile spasms (IS) in adult patients. We analyzed 214 children born between 1960 and 1976 who had been followed for 20-35 years or until death at 3 months to 30 years of age. Mortality was 31% (67 of 214 patients). Thirty-six of the surviving patients (24%) had normal (25 patients) or only slightly impaired (11 patients) intelligence as assessed by their educational abilities. Four had academic occupations. Eight were married or living unmarried with a partner. Five had healthy children. At follow-up, the EEGs of the 25 normal persons were either normal or slightly abnormal, demonstrated focal findings in 9 (36%), and had unspecific changes in 1. Focal abnormalities were not more common in patients with less good outcomes (37%). In patients with normal neurological outcomes, IS had been classified as cryptogenic only in 9 of 25 (36%) cases. Therefore, some patients with IS apparently have normal intelligence and socioeconomic status as adults, including patients whose spasms were either symptomatic or associated with focal EEG findings.

The Epidemiology and Treatment of Chronic and Refractory Epilepsy

Abstract: In developed countries, the incidence of epilepsy is 50-100 cases per 100,000 population per year and the prevalence is approximately 5 to 8 cases per 1,000 population. Epilepsy is by far the most prevalent serious neurologic condition. Mortality rates in epilepsy are two to four times those found in matched nonepileptic populations. The prognosis of epilepsy can be classified into at least four categories, with chronic and refractory cases comprising about 40% of all cases. A detailed approach to the management of chronic epilepsy cases is recommended. Approximately 20% of patients cannot achieve seizure control with existing agents and new antiepileptic drugs are required for these patients.

Safety of topiramate: adverse events and relationships to dosing.

Abstract: To date, 1,809 individuals have been exposed to topiramate (TPM), primarily adults with partial-onset seizures. Of this total, 665 patients have been treated for more than 1 year, 177 for more than 3 years, and 67 for more than 5 years. The profile of treatment-emergent adverse reactions (TEAEs) observed with TPM at various dosages is based primarily on data from five double-blind, placebo-controlled trials in which 360 patients received TPM at target doses of 200-1,000 mg/day. Long-term safety is assessed on the basis of 1,001 patients treated with TPM in controlled and open trials for up to 5.3 years. Most of the commonly reported TEAEs were related to the central nervous system and were observed with greater frequency at dosages above the 200-400-mg/day range found to be optimal in dose ranging trials. Nephrolithiasis not requiring surgery was seen in 1.5% of patients, and mild, dose-related weight loss was associated with TPM therapy. No clinically significant treatment-related abnormalities were observed in clinical laboratory parameters or in neurologic, electrocardiographic, ophthalmologic, or audiologic tests.

Double-Blind, Placebo-Controlled Trial of Topiramate (600 mg Daily) for the Treatment of Refractory Partial Epilepsy

Abstract: Purpose: We wished to evaluate adjunctive therapy for partial-onset seizures with topiramate (TPM) for efficacy and safety in a double-blind, placebo-controlled, randomized, parallel-group study.Methods: Sixty outpatients with epilepsy (47 men and 13 women, mean age 32.9 years) were studied. All had a documented history of partial-onset seizures with or without secondarily generalized seizures. After an 8-week baseline during which patients had at least one seizure per week, 30 patients each were randomized to TPM 300 mg twice daily (b.i.d.) or placebo for 12 weeks.Results: TPM was significantly superior to placebo, as indicated by all efficacy assessments: greater median percent reduction from baseline in the average monthly seizure rate (46 vs. - 12%, p = 0.004); greater number of treatment responders (patients with greater than or equal to 50% reduction in seizure rate) (47 vs. 10%, p = 0.001), and better investigator (p = 0.002) and patient (p = 0.010) global assessments of treatment. Among TPM-treated patients, the most commonly reported adverse events (AE) were headache, somnolence, fatigue, dizziness, and abnormal thinking, Most AE were mild or moderate in severity.Conclusions: The results of the present trial indicate that TPM 600 mg/day is effective in the treatment of refractory partial-onset seizures with or without secondarily generalized seizures.

Long‐Term Outcome After Epilepsy Surgery

Abstract: In considering the long-term outcome of patients undergoing epilepsy surgery, we are concerned not only with the effect on seizures, but also with the effect on quality of life (QOL). Interpreting published reports is difficult because of several methodological issues. First, there is no standard classification with regard to seizures or other aspects of outcome. Second, seizure outcome is almost always considered in terms of frequency, and severity is not assessed. Third, duration of follow-up varies considerably but is usually only 1-2 years. Because most patients at most centers have been operated on recently, most reports are skewed toward more recent outcomes, thus minimizing longer term changes. Fourth, surgical groups are commonly mixed and include patients with both extratempcral and temporal lobe epilepsy of diverse causes. Fifth, different surgeons use different operative techniques, and the extent of both temporal and extratemporal resections can vary greatly from center to center. Finally, patient selection and evaluation for various operative procedures has varied not only over time but among individual centers. Therefore, performing a meaningful analysis of the long-term outcome of a patient who has undergone epilepsy surgery is difficult. The only substantive study that compared epilepsy surgery patients with a matched group of medically treated patients with similarly refractory epilepsy suggests that there is some reason to be concerned about the outcome of epilepsy surgery. In 1991, Guldvog et al. published a retrospective, parallel, longitudinal cohort study of 185 medically managed and 201 surgically managed patients with uncontrolled epilepsy (1,2). The medical and surgical groups were matched for age, year at treatment and at diagnosis, seizure type and frequency, and neurological status. Patients had been followed for

Routine EEG and Temporal Lobe Epilepsy: Relation to Long‐Term EEG Monitoring, Quantitative MRI, and Operative Outcome

Abstract: Summary: Purpose: To investigate the relation among routine EEG, long-term EEG monitoring (LTM), quantitative magnetic resonance imaging (MRI), and surgical outcome in temporal lobe epilepsy (TLE). Methods: We evaluated 159 patients with intractable TLE who underwent an anterior temporal lobectomy between 1988 and 1993. The epileptogenic temporal lobe was determined by ictal LTM. A single awake-sleep outpatient EEG with standard activating procedures was performed before LTM. EEGs were analyzed by a blinded investigator. Results: MRI scans showed unilateral medial temporal atrophy (109 patients) or symmetrical hippocampal volumes (50 patients). The surgically excised epileptogenic brain tissue revealed mesial temporal sclerosis, gliosis, or no histopathologic alteration. Routine EEG revealed temporal lobe epileptiform discharges in 123 patients. Routine EEG findings correlated with the temporal lobe of seizure origin (p 0.20). Conclusions: Results of this study modified our approach in patients with TLE. Interictal epileptiform discharges localized to one temporal lobe on serial routine EEGs or during LTM may be adequate to identify the epileptogenic zone in patients with MRI-identified unilateral medial temporal lobe atrophy.

The ictal bradycardia syndrome

Abstract: Summary : Purpose: Episodic loss of consciousness presents a diagnostic challenge to the neurologist. A perhaps under-recognized cause of episodic loss of consciousness, which we call the ictal bradycardia syndrome, occurs when epileptic discharges profoundly disrupt normal cardiac rhythm, resulting in cardiogenic syncope during the ictal event. We attempt to determine whether the presence of the ictal bradycardia syndrome provides localizing information regarding the site of seizure onset and to describe the demographics of patients with this syndrome. We also discuss difficulties in diagnosis and treatment. Methods: We review 23 cases of the ictal bradycardia syndrome from the literature and present four additional cases. Brief histories are provided for the four previously unreported cases. Where data are available, cases are analyzed with respect to age, sex, and site of seizure onset. Results: Patients with the ictal bradycardia syndrome ranged from 4 months to 72 years (mean 39 years). There was an approximately 5:1 ratio of males to females. Twenty of the 23 patients (87%) whose site of ictal onset could be localized had temporal lobe epilepsy, although no clear lateralizing predominance was apparent. Conclusions: The ictal bradycardia syndrome should be considered in patients with unusual or refractory episodes of syncope, or in patients with a history suggestive of both epilepsy and syncope. It suggests seizure onset in temporal lobe, and is more commonly diagnosed in males. Diagnosis may be aided by ambulatory EEGECG monitoring. Cardiac pacemaker implantation along with antiepileptic drug therapy may be necessary to minimize the possibility of death.

On the Structure of Ictal Events in Vitro

Abstract: Summary: Purpose: To analyze the cellular and network mechanisms of sustained seizures, we reviewed the literature and present new data on in vitro epileptiform events. We considered single and recurring synchronized population bursts occurring on a time scale from tens of milliseconds to I min. Methods: We used intracellular and field potential recordings, together with computer network simulations, derived from three types of experimental epileptogenesis: γ-aminobutyric-acidA, (GABAA) blockade, low extracellular [Mg2+]0, and 4-aminopyridine (4-AP). Results: In all three models, sustained depolarizing synaptic currents developed, either through N-methyl-D-aspartate (NMDA) receptors, depolarizing GABAA, receptors, or both. Ectopic action potentials (APs), probably originating in axonal structures, occurred in 4-AP and (as shown by other researchers) after tetanic stimulation; ectopic APs, occurring at sufficient frequency. should also depolarize dendrites, by synaptic excitation, enough to trigger bursts. Conclusions: Ictal-like events appear to arise from two basic mechanisms. The first mechanism consists of sustained dendritic depolarization driving a series of dendritic bursts. The second mechanism consists of an increase in axonal and presynaptic terminal excitability driving a series of bursts analogous to interictal spikes.

Prevalence of epilepsy in the elderly: The Rotterdam study

Abstract: We assessed the prevalence of epilepsy in an elderly population in The Netherlands. The study was conducted from 1991 to 1993 as part of the Rotterdam Study, a population-based door-to-door study of all elderly people living in Ommoord, a suburb of Rotterdam, and included 5,559 persons aged 55-95 years. All subjects were screened for epilepsy through direct questions regarding the existence of epilepsy and antiepileptic drug (AED) use, in addition to relevant questions from the World Health Organization (WHO) protocol for epidemiologic studies of neurologic diseases. Further evaluation of screen positives was made by a panel of 1 study physician and 4 epileptologists, who also classified all confirmed cases of epilepsy according to the classifications of the International League Against Epilepsy (ILAE). The overall prevalence of active epilepsy in our study population was 0.9% including special syndromes and 0.8% excluding special syndromes. The prevalence increased with age from 0.7% for those aged 55-64 years to 1.2% for those aged 85-94 years. The increase with age was detected among men and women both. Our study confirms other findings showing that the prevalence of active epilepsy increases with age in the elderly. The prevalence figures in our study were high as compared with those of other population-based studies. Epilepsy appears to be a major cause of morbidity in the elderly.

Vagus nerve stimulation induces a sustained anticonvulsant effect

Abstract: Summary: Purpose: Stimulation of the vagus nerve can effectively abort several types of experimentally induced seizures in animals when administered near the time of seizure onset. Indirect evidence from human trials and animal studies suggests that the anticonvulsant effects of vagus nerve stimulation (VNS) extend beyond the duration of stimulation. We used the pentylenetetrazol model to determine whether VNS exerts a persistent anticonvulsant effect. Methods: VNS (1 mA, 30 Hz, 500 μs pulse width) was administered continuously for 0, 1, or 60 min, or intermittently (30 s on, 5 min off) for 60 min, to awake and freely moving animals. After the end of stimulation, pentylenetetrazol (50 mg/kg i.p.) was administered to induce seizures. Time-course studies were also performed, consisting of 60 min of VNS followed by pentylenetetrazol injection after 0, 3-, 5-, and 10-min intervals. Results: The greatest anticonvulsant effect occurred after 60 min of continuous VNS, which prevented convulsions in four of 12 rats and reduced significantly seizure duration, the total number of seizures, and number of tonic seizures. Intermittent VNS was less effective than continuous stimulation for 60 min, but more effective than that for 1 min. The anticonvulsant effect declined in a time-dependent fashion after discontinuation of VNS, with return to nonstimulated control values by 10 min. Conclusions: The results of this study verify a persistent VNS-induced anticonvulsant effect and indicate that its efficacy is dependent on the cumulative stimulus duration.

Concentrations and Effects of Oral Midazolam are Greatly Reduced in Patients Treated with Carbamazepine or Phenytoin

Abstract: Midazolam is a short-acting benzodiazepine which is used as an oral hypnotic agent in several countries. We studied the pharmacokinetic and pharmacodynamic aspects of an oral 15-mg dose of midazolam in 6 patients with epilepsy who are also taking carbamazepine (CBZ) or phenytoin (PHT). We compared results with those obtained in 7 noninduced control subjects. Plasma concentrations and effects of midazolam were measured for 10 h. In patients with epilepsy, the area under the plasma concentration-time curve (AUC) of midazolam (mean +/- SEM) was only 5.7% (0.60 +/- 0.16 vs. 10.5 +/- 0.6 microgram x min/ml), and the peak midazolam concentration was 7.4% (5.2 +/- 1.2 vs. 70.4 +/- 9.0 ng/ml) of its value in control subjects (p < 0.001). The elimination half-life (t l/2) of midazolam was 1.3 +/- 0.2 h in patients and 3.1 +/- 0.1 h in controls (p < 0.001). The low plasma midazolam concentrations in the patient group were associated with reduced pharmacodynamic effects as compared with control subjects [e.g., the Critical Flicker Fusion Test (CFFT), p < 0.05]. Induction of CYP3A (cytochrome P-450IIIA) enzymes by CBZ and PHT is the most likely explanation of the great difference in the pharmacokinetic and pharmacodynamic profiles of oral midazolam in the two groups.